Studies show leptin restores ovulation in some women

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BOSTON — An appetite-curbing hormone that failed to live up to its early buzz as a possible key to slowing obesity is now being probed as a potential aid for women who suffer from infertility and eating disorders.

Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

“This represents essentially a new era for leptin,” said Dr. Jean Chan, one of the researchers exploring new uses for the hormone. “Now that we understand so much more about what this hormone does, we can target it appropriately for the right condition.”

A very small study, led by researchers at the Beth Israel Deaconess Medical Center and at Massachusetts General Hospital and published recently in the New England Journal of Medicine, found that leptin restored menstrual periods in a few female athletes who hadn’t had periods for an average of 5½ years.

Authors of the study also said there were some preliminary signs that the hormone improved bone density, which begins to decline when women stop menstruating.

Women with low body fat, including athletes and those with eating disorders, often stop menstruating, developing a condition called hypothalamic amenorrhea.

The condition, caused by the way the brain regulates the reproductive system, can also affect some women who are simply thin or even of normal weight. Doctors believe stress may be to blame for some cases, while others may be due to changes in body composition from diet and exercise.

One function of leptin, which was discovered in 1994, is to regulate appetite. It was originally thought that increasing leptin might suppress the appetites of obese people. But studies found heavy people tended to have plenty of leptin and adding more didn’t help.

Researchers in the new study, which was funded by institutional grants and Amgen, the developer of a drug based on the hormone, began looking at people who may not have enough leptin because of low body fat.

The researchers gave injections of Amgen’s synthetic leptin to eight competitive women athletes, all with hypothalamic amenorrhea. The injections raised the women’s leptin levels to those of normal women or higher. Treatment was given until they responded or up to three months, whichever came first. (One woman dropped out of the study.)

Five of the remaining seven showed promising results, according to the study. Three of the women, one of whom had not had a period in 14 years, ovulated and had menstrual bleeding. Two others were “for all intents and purposes about to ovulate,” Chan said.

Researchers said they envisioned possible fertility treatments, help for thin athletes at risk of bone fractures, and restoration of menstruation to patients recovering from anorexia.

Dr. Barbara Corkey, president of the North American Association for the Study of Obesity and a professor of medicine and biochemistry at Boston University, said the study had found a “creative use of leptin,” but she wasn’t surprised.

“Leptin doesn’t have only one function,” she said. “It serves another function and this highlights that.”

Dr. William Schlaff, president of the Society for Reproductive Endocrinology and Infertility and a professor at the University of Colorado Health Sciences Center in Denver, said the study was “very nicely designed” and had made an “important first observation” that needed further study. Ultimately, he speculated, it could lead to advances that would help infertile women.

Dr. Rexford Ahima, at the University of Pennsylvania School of Medicine’s Division of Endocrinology, Diabetes and Metabolism, said the study suggested that leptin is the signal that links fat tissue to the brain and instructs it to control menstruation.

Ahima agreed that leptin might have potential as a fertility treatment. But he had questions about its use as a treatment for eating disorders, noting that anorexia is primarily a psychiatric disorder whose root cause should be addressed before leptin is considered.

Chan, at the Beth Israel medical center, said researchers are already planning a longer study of a larger group of women.